**5. Oral glucose tolerance test (OGTT): undeniably the best choice investigation for dysglycaemia**

The OGTT is a non-physiological procedure required to unveil a highly compensated derangement in insulin's handling of glucose metabolism [62]. It requires administration of glucose solution to a patient who has indication for investigation of glucose dysmetabolism. Although more sensitive diagnostic test than FPG, the OGTT is affected by a number of factors that result in less acceptable reproducibility. Therefore OGTT requires that any influence in glucose handling must be eliminated or minimize where result should reflect patient's internal milieu, to increase reproducibility. Subsequently, patient preparation, a forvarable atmosphere during the procedure, standardized sampling protocol, sample handling, and analysis are paramount. OGTT or 2-hr post-glucose levels do indicates the pathophysiology responsible for diabetes better than any other glycaemic parameter as it provides information on what happens in the postprandial state, when glucose is high in the system and when the functional capacity of pancreatic β-cell is crucial. Normal blood glucose levels 2-hr after glucose load indicates a good β-cell capacity, whereas high levels document an impairment of β-cell function [63]. This means that only 2 hr OGTT PG can provide reliable information on the key pathophysiological defect of dysglycaemia or providing advice regarding the correct therapy to overcome it.

#### **5.1 Advantages of OGTT in screening for dysglycaemia**

The oral glucose tolerance test has a long history [64] but from time to time had to endure considerable criticism. One review pointed out that the considerable number of variables involved results in both poor reproducibility and difficulties in interpretation [65]. In spite of this the oral glucose tolerance test survives and for routine use in the diagnosis of diabetes mellitus it is not replaceable (Undeniably). The OGTT detects changes in post-prandial glycaemia that tend to precede changes in fasting glucose. In fact, inability to respond appropriately to a glucose challenge, i.e., glucose intolerance, represents the fundamental pathologic defect in diabetes mellitus and OGTT is currently the gold standard for the diagnosis of diabetes. The OGTT is vital for the characterization of metabolic syndrome, the metabolic actions of cardiovascular and metabolic drugs, and natural progression from prediabetes to T2DM. OGTT is extensively used as a sensitive indicator of GDM. Therefore, OGTT is an important Lab tool in preclinical studies as it provides an indication of the relative roles of insulin secretion and insulin resistance in the progression of glucose intolerance.

The OGTT allows all of the normal stages of insulin secretion and glucose processing to take place in sequence without causing stress or trauma to the subject. The OGTT is the most robust means of establishing the diagnosis of diabetes and provides a more comprehensive assessment of dynamic glucose handling. Thus, the OGTT more accurately mirrors daily life. OGTT is much more sensitive in identifying the loci of insulin resistance and its modulation by different interventions. Thus, the OGTT is useful as a research tool, yields laboratory data with greater relevance to the prevention and treatment of human disease. It is the reference method for the assessment of glucose tolerance, despite the notoriously poor

#### *Oral Glucose Tolerance Test (OGTT): Undeniably the First Choice Investigation… DOI: http://dx.doi.org/10.5772/intechopen.96549*

reproducibility of the test (CV = 50%) for 2 h blood glucose. Some of these cause of variations can be minimized with adequate attention to physical activities, dietary preparation and taking care of sample collection at the 2-hr sample (sampling must be done within 5 minutes of 120 minute [66]. The WHO (1999) placed emphasis on the OGTT as the "gold standard", with both fasting and 120-min values being taken into consideration [67]**.** This is by no means a mistake. Only when an OGTT cannot be performed should the diagnosis rely on fasting levels. Other hormones and metabolites can be measured during OGTT, not just glucose and insulin, eg., the OGTT is the primary test used for the diagnosis of GH hypersecretion.

OGTT is the only means of identifying people with IGT, and IGT is an essential diagnostic step, especially when FPG is within the normal range, as these subjects are at high risk not only for type 2 diabetes, but in particular for cardiovascular disease. The main clinical significance of IGT are [68]: (1) It is a risk factor for type 2 diabetes, about 20–50% of subjects with IGT develop type 2 diabetes over 10 years; (2) It predisposes individual to cardiovascular disease (CVD); and (3) It is a component of the metabolic syndrome and its consequences. IGT when identified and subsequently managed will prevent or delayed progression to type 2 diabetes mellitus. It has been indicated by recent studies [69–71] that persons classified with IGT using WHO criteria have increased risk of cardiovascular disease, however many of these subjects do not have impaired fasting glucose (IFG) by the new ADA criteria. Furthermore, the OGTT by WHO criteria identifies diabetes in 2% more individuals than does FPG using ADA criteria [70], although diabetic individuals who are identified by both abnormal FPG and 2-h OGTT have a higher risk of premature death than those with only an increased FPG concentration [71]. More so, fasting plasma glucose alone fails to diagnose in about 30% of cases of diabetes diagnosed by OGTT. OGTT establishes whether an IFG subjects has normal 2hPG and only the simultaneous information obtained from 2hPG (OGTT) allows the screening to become effective. An important matter here is that people with IGT who cannot be identified by either FPG or A1c have ≈40% increased mortality compared with normoglycaemic subjects and lifestyle intervention in these individuals can prevents progression to type 2 diabetes and may reduce their mortality risk to the level observed among normoglycaemic population. These prevention benefits do not exist for A1c or FPG, and this evidences should not be forgotten when deciding the approaches to identify intermediate dysglycaemia. We should therefore make OGTT a priority in an attempt to diagnose hyperglycaemia as early as possible.

Thus, using solely FPG, would deceitfully reassure a large proportion of individuals as having NGT, without warning them on the benefits of preventive treatment. Epidemiological studies showed that A1c and plasma glucose (FPG and/or 2-hr OGTT) identify partially different groups of diabetic subjects. While A1c ≥6.5% identifies only ≈30–40% newly diagnosed patients with diabetes [72], a larger percentage was detected by FPG (≈50%), and more so by 2-hr PG(≈90%).

These findings are based on several recent studies, including the 2003–2006 NHANES study demonstrating only 30% of diabetic individuals were detected by A1c ≥6.5%, 46% by PFG ≥126 mg/dl, and the IRAS demonstrated 32%, 45%, and 87%, respectively) [73] indicating OGTT is superior. However, the pivotal issue on OGTT is its low reproducibility which is significantly represented by physiologic contexts of the test. The plasma glucose during OGTT are influenced by both insulin sensitivity and secretion, however, impact of other factors particularly incretins, neural responses to nutrient ingestion, gastrointestinal motility and gastric emptying are also important. These factors differ significantly between individuals and are part of non-modifiable factors that govern post-load glucose metabolism and plasma glucose concentration, and are difficult to measure in every

In conclusion, although in clinical practice the OGTT is often regarded as a cumbersome, time-consuming, and patient-unfriendly procedure, for a more detailed and sensitive assessment of the glucose dysmetabolism, the oral glucose

**5. Oral glucose tolerance test (OGTT): undeniably the best choice**

The OGTT is a non-physiological procedure required to unveil a highly compensated derangement in insulin's handling of glucose metabolism [62]. It requires administration of glucose solution to a patient who has indication for investigation of glucose dysmetabolism. Although more sensitive diagnostic test than FPG, the OGTT is affected by a number of factors that result in less acceptable reproducibility. Therefore OGTT requires that any influence in glucose handling must be eliminated or minimize where result should reflect patient's internal milieu, to increase reproducibility. Subsequently, patient preparation, a forvarable atmosphere during the procedure, standardized sampling protocol, sample handling, and analysis are paramount. OGTT or 2-hr post-glucose levels do indicates the pathophysiology responsible for diabetes better than any other glycaemic parameter as it provides information on what happens in the postprandial state, when glucose is high in the system and when the functional capacity of pancreatic β-cell is crucial. Normal blood glucose levels 2-hr after glucose load indicates a good β-cell capacity, whereas high levels document an impairment of β-cell function [63]. This means that only 2 hr OGTT PG can provide reliable information on the key pathophysiological defect of dysglycaemia or providing advice regarding the correct therapy to overcome it.

The oral glucose tolerance test has a long history [64] but from time to time had

to endure considerable criticism. One review pointed out that the considerable number of variables involved results in both poor reproducibility and difficulties in interpretation [65]. In spite of this the oral glucose tolerance test survives and for routine use in the diagnosis of diabetes mellitus it is not replaceable (Undeniably). The OGTT detects changes in post-prandial glycaemia that tend to precede changes in fasting glucose. In fact, inability to respond appropriately to a glucose challenge, i.e., glucose intolerance, represents the fundamental pathologic defect in diabetes mellitus and OGTT is currently the gold standard for the diagnosis of diabetes. The OGTT is vital for the characterization of metabolic syndrome, the metabolic actions of cardiovascular and metabolic drugs, and natural progression from prediabetes to T2DM. OGTT is extensively used as a sensitive indicator of GDM. Therefore, OGTT is an important Lab tool in preclinical studies as it provides an indication of the relative roles of insulin secretion and insulin resistance in the progression of glucose

The OGTT allows all of the normal stages of insulin secretion and glucose processing to take place in sequence without causing stress or trauma to the subject. The OGTT is the most robust means of establishing the diagnosis of diabetes and provides a more comprehensive assessment of dynamic glucose handling. Thus, the OGTT more accurately mirrors daily life. OGTT is much more sensitive in identifying the loci of insulin resistance and its modulation by different interventions. Thus, the OGTT is useful as a research tool, yields laboratory data with greater relevance to the prevention and treatment of human disease. It is the reference method for the assessment of glucose tolerance, despite the notoriously poor

tolerance test (OGTT) is the best.

**investigation for dysglycaemia**

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

**5.1 Advantages of OGTT in screening for dysglycaemia**

intolerance.

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individual undergoing OGTT. Finally, all trials aimed at type 2 diabetes prevention included IGT subjects [74, 75], who could not be possibly recognised without OGTT, seems therefore evident that the routine execution of OGTT is presently the one and only possible answer (Undeniably) [76].
